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PubMed | University of Padua, Medical University-Sofia, University Hospital Ospedali Riuniti, Hospital Clinico San Carlos IdISSC and 14 more.
Type: Journal Article | Journal: The Journal of allergy and clinical immunology | Year: 2016

Anaphylaxis in children and adolescents is a potentially life-threatening condition. Its heterogeneous clinical presentation and sudden occurrence in virtually any setting without warning have impeded a comprehensive description.We sought to characterize severe allergic reactions in terms of elicitors, symptoms, emergency treatment, and long-term management in European children and adolescents.The European Anaphylaxis Registry recorded details of anaphylaxis after referral for in-depth diagnosis and counseling to 1 of 90 tertiary allergy centers in 10 European countries, aiming to oversample the most severe reactions. Data were retrieved from medical records by using a multilanguage online form.Between July 2007 and March 2015, anaphylaxis was identified in 1970 patients younger than 18 years. Most incidents occurred in private homes (46%) and outdoors (19%). One third of the patients had experienced anaphylaxis previously. Food items were the most frequent trigger (66%), followed by insect venom (19%). Cows milk and hens egg were prevalent elicitors in the first 2 years, hazelnut and cashew in preschool-aged children, and peanut at all ages. There was a continuous shift from food- to insect venom- and drug-induced anaphylaxis up to age 10 years, and there were few changes thereafter. Vomiting and cough were prevalent symptoms in the first decade of life, and subjective symptoms (nausea, throat tightness, and dizziness) were prevalent later in life. Thirty percent of cases were lay treated, of which 10% were treated with an epinephrine autoinjector. The fraction of intramuscular epinephrine in professional emergency treatment increased from 12% in 2011 to 25% in 2014. Twenty-six (1.3%) patients were either admitted to the intensive care unit or had grade IV/fatal reactions.The European Anaphylaxis Registry confirmed food as the major elicitor of anaphylaxis in children, specifically hens egg, cows milk, and nuts. Reactions to insect venom were seen more in young adulthood. Intensive care unit admissions and grade IV/fatal reactions were rare. The registry will serve as a systematic foundation for a continuous description of this multiform condition.


PubMed | Karolinska Institutet, Hospital Clinico San Carlos IdISSC, James Cook University, University of Zürich and 43 more.
Type: | Journal: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology | Year: 2016

The availability of allergen molecules (components) from several protein families has advanced our understanding of immunoglobulin E (IgE)-mediated responses and enabled component-resolved diagnosis (CRD). The European Academy of Allergy and Clinical Immunology (EAACI) Molecular Allergology Users Guide (MAUG) provides comprehensive information on important allergens and describes the diagnostic options using CRD. Part A of the EAACI MAUG introduces allergen molecules, families, composition of extracts, databases, and diagnostic IgE, skin, and basophil tests. Singleplex and multiplex IgE assays with components improve both sensitivity for low-abundance allergens and analytical specificity; IgE to individual allergens can yield information on clinical risks and distinguish cross-reactivity from true primary sensitization. Part B discusses the clinical and molecular aspects of IgE-mediated allergies to foods (including nuts, seeds, legumes, fruits, vegetables, cereal grains, milk, egg, meat, fish, and shellfish), inhalants (pollen, mold spores, mites, and animal dander), and Hymenoptera venom. Diagnostic algorithms and short case histories provide useful information for the clinical workup of allergic individuals targeted for CRD. Part C covers protein families containing ubiquitous, highly cross-reactive panallergens from plant (lipid transfer proteins, polcalcins, PR-10, profilins) and animal sources (lipocalins, parvalbumins, serum albumins, tropomyosins) and explains their diagnostic and clinical utility. Part D lists 100 important allergen molecules. In conclusion, IgE-mediated reactions and allergic diseases, including allergic rhinoconjunctivitis, asthma, food reactions, and insect sting reactions, are discussed from a novel molecular perspective. The EAACI MAUG documents the rapid progression of molecular allergology from basic research to its integration into clinical practice, a quantum leap in the management of allergic patients.


PubMed | Reykjavik University, University of Manchester, Hospital Clinico San Carlos IdISSC, University of Groningen and 7 more.
Type: | Journal: Allergy | Year: 2016

The conduct of oral food challenges as the preferred diagnostic standard for food allergy (FA) was harmonized over the last years. However, documentation and interpretation of challenge results, particularly in research settings, are not sufficiently standardized to allow valid comparisons between studies. Our aim was to develop a diagnostic toolbox to capture and report clinical observations in double-blind placebo-controlled food challenges (DBPCFC).A group of experienced allergists, paediatricians, dieticians, epidemiologists and data managers developed generic case report forms and standard operating procedures for DBPCFCs and piloted them in three clinical centres. The follow-up of the EuroPrevall/iFAAM birth cohort and other iFAAM work packages applied these methods.A set of newly developed questionnaire or interview items capture the history of FA. Together with sensitization status, this forms the basis for the decision to perform a DBPCFC, following a standardized decision algorithm. A generic form including details about severity and timing captures signs and symptoms observed during or after the procedures. In contrast to the commonly used dichotomous outcome FA vs no FA, the allergy status is interpreted in multiple categories to reflect the complexity of clinical decision-making.The proposed toolbox sets a standard for improved documentation and harmonized interpretation of DBPCFCs. By a detailed documentation and common terminology for communicating outcomes, these tools hope to reduce the influence of subjective judgment of supervising physicians. All forms are publicly available for further evolution and free use in clinical and research settings.


Worm M.,Charité - Medical University of Berlin | Scherer K.,University of Basel | Lang R.,Paracelsus Medical University | Fernandez-Rivas M.,Hospital Clinico San Carlos IdISSC | And 14 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2014

Methods: Tertiary allergy, dermatology and paediatric units in 10 European countries took part in this pilot phase of the first European Anaphylaxis Registry, from June 2011 to March 2014. An online questionnaire was used to collect data on severe allergic reactions based on the medical history and diagnostics.Results: Fifty-nine centres reported 3333 cases of anaphylaxis, with 26.7% below 18 years of age. Allergic reactions were mainly caused by food (children and adults 64.9% and 20.2%, respectively) and insect venom (20.2% and 48.2%) and less often by drugs (4.8% and 22.4%). Most reactions occurred within 30 min of exposure (80.5%); a delay of 4+ hours was mainly seen in drug anaphylaxis (6.7%). Symptom patterns differed by elicitor, with the skin being affected most often (84.1%). A previous, usually milder reaction to the same allergen was reported by 34.2%. The mainstay of first-line treatment by professionals included corticoids (60.4%) and antihistamines (52.8%). Only 13.7% of lay-or self-treated reactions to food and 27.6% of insect anaphylaxis received on-site adrenaline.Conclusion: This pilot phase of a pan-European registry for severe allergic reactions provides for the first time data on anaphylaxis throughout Europe, demonstrates its potential functionality and allows a comparison of symptom patterns, elicitors and treatment habits between referral centres and countries.Background: Occurrence, elicitors and treatment of severe allergic reactions are recognized and reported differently between countries. We aimed to collect standardized data throughout Europe on anaphylaxis referred for diagnosis and counselling. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Herrero-Vanrell R.,Complutense University of Madrid | Herrero-Vanrell R.,Hospital Clinico San Carlos IdISSC | Bravo-Osuna I.,Complutense University of Madrid | Bravo-Osuna I.,Hospital Clinico San Carlos IdISSC | And 6 more authors.
Progress in Retinal and Eye Research | Year: 2014

Pathologies affecting the posterior segment of the eye are one of the major causes of blindness in developed countries and are becoming more prevalent due to the increase in society longevity. Successful therapy of diseases affecting the back of the eye requires effective concentrations of the active substance maintained during a long period of time in the intraocular target site. Treatment of vitreoretinal diseases often include repeated intravitreous injections that are associated with adverse effects. Local administration of biodegradable microspheres offers an excellent alternative to multiple administrations, as they are able to deliver the therapeutic molecule in a controlled fashion. Furthermore, injection of microparticles is performed without the need for surgical procedures. As most of the retinal diseases are multifactorial, microspheres result especially promising because they can be loaded with more than one active substance and complemented with the inclusion of additives with pharmacological properties. Personalized therapy can be easily achieved by changing the amount of administered microspheres. Contrary to non-biodegradable devices, biodegradable PLA and PLGA microspheres disappear from the site of administration after delivering the drug. Furthermore, microspheres prepared from these mentioned biomaterials are well tolerated after periocular and intravitreal injections in animals and humans. After injection, PLA and PLGA microspheres suffer aggregation behaving like an implant. Biodegradable microspheres are potential tools in regenerative medicine for retinal repair. According to the reported results, presumably a variety of microparticulate formulations for different ophthalmic therapeutic uses will be available in the clinical practice in the near future. © 2014.


Velasco G.,Complutense University of Madrid | Velasco G.,Research Center Biomedica en Red Sobre Enfermedades Neurodegenerativas | Velasco G.,Hospital Clinico San Carlos IdISSC | Sanchez C.,Complutense University of Madrid | And 3 more authors.
Nature Reviews Cancer | Year: 2012

Various reports have shown that cannabinoids (the active components of marijuana and their derivatives) can reduce tumour growth and progression in animal models of cancer, in addition to their well-known palliative effects on some cancer-associated symptoms. This Opinion article discusses our current understanding of cannabinoids as antitumour agents, focusing on recent insights into the molecular mechanisms of action, including emerging resistance mechanisms and opportunities for combination therapy approaches. Such knowledge is required for the optimization of preclinical cannabinoid-based therapies and for the preliminary clinical testing that is currently underway. © 2012 Macmillan Publishers Limited. All rights reserved.


PubMed | Hospital Clinico Of Valladolid, Hospital Clinico San Carlos IdISSC, Hospital Of Leon and Hospital Reina Sofia Of Cordoba
Type: Journal Article | Journal: Revista espanola de cardiologia (English ed.) | Year: 2016

The Working Group on Cardiac Catheterization and Interventional Cardiology presents its annual report on the data from the registry of the activityin 2015.All Spanish hospitals with catheterization laboratories were invited to voluntarily contribute their activity data. The information was collected online and analyzed mostly by an independent company.In 2015, 106 centers participated in the national register; 73 of these centers are public. A total of 145836 diagnostic studies were conducted, among which 128669 were coronary angiograms. These figures are higher than in previous years. The Spanish average of total diagnoses per million population was 3127. The number of coronary interventional procedures was very similar (67671), although there was a slight increase in the complexity of coronary interventions: 7% in multivessel treatment and 8% in unprotected left main trunk treatment. A total of 98043 stents were implanted, of which 74684 were drug-eluting stents. A total of 18418 interventional procedures were performed in the acute myocardial infarction setting, of which 81.9% were primary angioplasties. The radial approach was used in 73.3% of the diagnostic procedures and in 76.1% of interventional ones. The number of transcatheter aortic valve implantations continued to increase (1586), as well as the number of left atrial appendage closures (331).An increase in diagnostic and therapeutic procedures in acute myocardial infarction was reported in 2015. The use of the radial approach and drug-eluting stents also increased in therapeutic procedures. The progressive increase in structural procedures seen in previous years continued.


Maia V.,University of Salamanca | Ortiz-Rivero S.,University of Salamanca | Sanz M.,University of Salamanca | Gutierrez-Berzal J.,University of Salamanca | And 5 more authors.
Cell Communication and Signaling | Year: 2013

Background: Previous studies by our group and others have shown that C3G interacts with Bcr-Abl through its SH3-b domain. Results: In this work we show that C3G and Bcr-Abl form complexes with the focal adhesion (FA) proteins CrkL, p130Cas, Cbl and Abi1 through SH3/SH3-b interactions. The association between C3G and Bcr-Abl decreased upon Abi1 or p130Cas knock-down in K562 cells, which suggests that Abi1 and p130Cas are essential partners in this interaction. On the other hand, C3G, Abi1 or Cbl knock-down impaired adhesion to fibronectin, while p130Cas silencing enhanced it. C3G, Cbl and p130Cas-SH3-b domains interact directly with common proteins involved in the regulation of cell adhesion and migration. Immunoprecipitation and immunofluorescence studies revealed that C3G form complexes with the FA proteins paxillin and FAK and their phosphorylated forms. Additionally, C3G, Abi1, Cbl and p130Cas regulate the expression and phosphorylation of paxillin and FAK. p38α MAPK also participates in the regulation of adhesion in chronic myeloid leukemia cells. It interacts with C3G, CrkL, FAK and paxillin and regulates the expression of paxillin, CrkL and α5 integrin, as well as paxillin phosphorylation. Moreover, double knock-down of C3G/p38α decreased adhesion to fibronectin, similarly to the single silencing of one of these genes, either C3G or p38α. These suggest that C3G and p38α MAPK are acting through a common pathway to regulate cell adhesion in K562 cells, as previously described for the regulation of apoptosis. Conclusions: Our results indicate that C3G-p38αMAPK pathway regulates K562 cell adhesion through the interaction with FA proteins and Bcr-Abl, modulating the formation of different protein complexes at FA. © 2013 Maia et al; licensee BioMed Central Ltd.

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